The adverse effects of alcohol on Central Nervous System development and underlying mechanisms causing these effects have been the subject of numerous studies [reviewed by7] Some proposed mechanisms to account for these deficits include altered placental transport, diminished neurotransmitter function, hypoxia, and disruption of neurotransmitter-gated ion channels, as well as many others. Another possible mechanism that has received limited focus is the effect(s) of alcohol on the synthesis, functioning, and/or expression of proteins associated with neuronal growth and survival. One such protein is S 100B, a Ca 2+- binding astrocytic protein that has been postulated to be both a neurotrophic (promotes neuronal survival) and a neurotropic (supports neurite outgrowth) agent. It also regulates the phosphorylation of other brain proteins, binds Ca z+, and promotes astrocytic mitogenesis--all activities that are important in proper neuronal development and function. Prenatal alcohol exposure is linked to decreased neuron numbers in the hippocampus of rodents. This observed effect could be the result of the direct action of alcohol on proteins such as S 100B that are involved in growth processes. To begin to address these issues, the dose responsiveness and critical time(s) of ethanol exposure will be established for the expression pattern and/or levels of S100B following prenatal ethanol exposure in offspring. Additionally, because it is not known whether S 100B is affected during earlier times of exposure than used to gather preliminary data (i.e., PD 60), the effect(s) of prenatal ethanol exposure on S 100B expression and/or levels will be assessed at various time points during development. It is believed that completion of the specific aims set forth in the following proposal will help further our fundamental understanding of how prenatal alcohol exposure may alter fetal hippocampal development. Furthermore, these findings should have both clinical and basic science research relevance since the hippocampus is widely considered to be actively involved in learning and memory, processes which can be adversely affected following prenatal ethanol exposure.